Carbon nanohoops and methods of making

ABSTRACT

The present invention provides cycloparaphenylene compounds, their macrocyclic precursors, and methods for making the compounds. The cycloparaphenylene compounds can be used to prepare armchair carbon nanotubes.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.61/266,667, filed Dec. 4, 2009, which is incorporated in its entiretyherein for all purposes.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH AND DEVELOPMENT

This invention was made with Government support under Grant No.DE-AC02-05CH11231, awarded by the U.S. Department of Energy. TheGovernment has certain rights in this invention.

BACKGROUND OF THE INVENTION

Carbon nanotubes (also herein referred to as CNTs) are very smalltube-shaped structures essentially having a composition of a graphitesheet in a tubular form. Carbon nanotubes have interesting andpotentially useful electrical and mechanical properties and offerpotential for various uses in electronic devices. Carbon nanotubes alsofeature extremely high electrical conductivity, very small diameters(much less than 100 nanometers), large aspect ratios (i.e.length/diameter ratios) (greater than 1000), and a tip-surface area nearthe theoretical limit (the smaller the tip-surface area, the moreconcentrated the electric field, and the greater the field enhancementfactor). These features make carbon nanotubes ideal candidates forelectron field emitters, white light sources, lithium secondarybatteries, hydrogen storage cells, transistors, and cathode ray tubes(CRTs).

Generally, there are three methods for manufacturing carbon nanotubes.The first method is the arc discharge method, which was first discoveredand reported in an article by Sumio lijima, entitled “HelicalMicrotubules of Graphitic Carbon” (Nature, Vol. 354, Nov. 7, 1991, pp.56-58). The second method is the laser ablation method, which wasreported in an article by T. W. Ebbesen et al., entitled “Large-scaleSynthesis of Carbon Nanotubes” (Nature, Vol. 358, 1992, pp. 220). Thethird method is the chemical vapor deposition (CVD) method, which wasreported in an article by W. Z. Li, entitled “Large-scale Synthesis ofAligned Carbon Nanotubes” (Science, Vol. 274, 1996, pp. 1701).

In order to use the carbon nanotubes more widely and more effectively,it is necessary to implement a controlled growth of the carbon nanotubeswith desired structural parameters. An alternative method of preparingcarbon nanotubes is to use a seed or template form of the CNT to beprepared and grow the CNT from the seed or template. Based on the seedor template selected, only the specific CNT would be prepared. Forexample, using a macrocycle of cycloparaphenylene as a template,armchair CNTs can be prepared under suitable conditions. Thecycloparaphenylenes are the smallest unit of an armchair CNT and, thus,can be used as seeds or templates to prepare large quantities of carbonnanotubes having specific electronic properties. What is needed,however, is a method of making the cycloparaphenylenes. Surprisingly,the present invention meets this and other needs.

BRIEF SUMMARY OF THE INVENTION

In some embodiments, the present invention provides cycloparaphenylenecompounds of formula I:

Each R group of formula I can independently be hydrogen, C₁₋₆ alkyl,C₃₋₈ cycloalkyl or aryl. Alternatively, two R groups on adjacent carbonscan be combined with the atoms to which each is attached to form a C₅₋₈cycloalkyl or an aryl. In addition, subscript n of formula I can be aninteger from 6 to 30.

In another embodiment, the present invention also provides compounds offormula II:

Each R¹ of formula II can be hydrogen, C₁₋₆ alkyl, C₁₋₆ heteroalkyl,C₃₋₈ cycloalkyl, heterocycloalkyl, aryl or heteroaryl. Moreover,subscript m can be an integer from 2 to 10.

In other embodiments, the present invention provides compounds offormula III:

Each R¹ of formula III can be as defined above. Moreover, each R² canindependently be a halogen or a boronate.

In some other embodiments, the present invention provides a method ofpreparing a compound of formula I. In formula I, each R can be hydrogen,and subscript n can be an integer of 6, 9, 12, 15, 18, 21, 24, 27 or 30.The method includes the step of contacting a reducing agent and acompound of formula II, where each R¹ can be hydrogen, C₁₋₆ alkyl, C₁₋₆heteroalkyl, C₃₋₈ cycloalkyl, heterocycloalkyl, aryl or heteroaryl, andsubscript m can be an integer from 2 to 10. Thus, the compound offormula I is prepared.

In still other embodiments, the present invention provides a method ofpreparing a compound of formula IIa:

In formula IIa, each R¹ can independently be hydrogen, C₁₋₆ alkyl, C₁₋₆heteroalkyl, C₃₋₈ cycloalkyl, heterocycloalkyl, aryl or heteroaryl. Eachdashed line of formula IIa can optionally be a bond, and subscript m canbe an integer from 2 to 10. The method of preparing a compound offormula IIa includes contacting a plurality of compounds of formulaIIIa:

where each R² can independently be a halogen or a boronate. Thus, thecompound of formula IIa is prepared.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows preparation of macrocyclic precursors of the presentinvention by first reacting 1,4-diiodobenzene with benzoquinone,followed by alkylation of the hydroxyl groups with methyliodide, toafford compound 4, a compound of formula III. Some of compound 4 is thenreacted with a borate to convert the iodide groups to boronate 5.Compounds 4 and 5 are then coupled to form cyclic precursors includingcompounds 6, 7 and 8.

FIG. 2 shows preparation of cycloparaphenylenes 9, 10 and 11 viaaromatization of compounds 6, 7 and 8 using lithium naphthalenide as aone-electron reductant.

FIG. 3 shows images of compounds 9 (9-membered ring), 10 (12-memberedring) and 11 (18-membered ring) in the solid (amorphous) form, solids of9, 10 and 11 irradiated with light at 365 nm, and solutions of 9, 10 and11 irradiated with light at 365 nm.

DETAILED DESCRIPTION OF THE INVENTION I. General

The present invention provides cycloparaphenylenes and methods formaking. Also provided are the corresponding macrocyclic precursors andmethods for making. The cycloparaphenylenes are the smallest fragment ofan armchair (metallic) carbon nanotube and are useful as templates forthe preparation of carbon nanotubes, as dyes, and as sensors for thecomplexation of other agents.

II. Definitions

As used herein, the term “alkyl” refers to a straight or branched,saturated, aliphatic radical having the number of carbon atomsindicated. For example, C₁-C₆ alkyl includes, but is not limited to,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, hexyl, etc. Other alkyl groups include,but are not limited to heptyl, octyl, nonyl, decyl, etc. Alkyl caninclude any number of carbons, such as 1-2, 1-3, 1-4, 1-5, 1-6, 1-7,1-8, 1-9, 1-10, 2-3, 2-4, 2-5, 2-6, 3-4, 3-5, 3-6, 4-5, 4-6 and 5-6. Thealkyl group is typically monovalent, but can be divalent, such as whenthe alkyl group links two moieties together.

The term “lower” referred to above and hereinafter in connection withorganic radicals or compounds respectively defines a compound or radicalwhich can be branched or unbranched with up to and including 7,preferably up to and including 4 and (as unbranched) one or two carbonatoms.

Substituents for the alkyl and heteroalkyl radicals (including thosegroups often referred to as alkylene, alkenyl, heteroalkylene,heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, andheterocycloalkenyl) can be one or more of a variety of groups selectedfrom, but not limited to: —OR′, ═O, ═NR′, ═N—OR′, —NR′R″, —SR′,-halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′, —CO₂R′, —CONR′R″, —OC(O)NR′R″,—NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O)₂R′, —NR—C(NR′R″R′″)═NR″″,—NR—C(NR′R″)═NR′″, —S(O)R′, —S(O)₂R′, —S(O)₂NR′R″, —NRSO₂R′, —CN and—NO₂ in a number ranging from zero to (2m′+1), where m′ is the totalnumber of carbon atoms in such radical. R′, R″, R′″ and R″″ eachpreferably independently refer to hydrogen, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted aryl, e.g., aryl substitutedwith 1-3 halogens, substituted or unsubstituted alkyl, alkoxy orthioalkoxy groups, or arylalkyl groups. When a compound of the inventionincludes more than one R group, for example, each of the R groups isindependently selected as are each R′, R″, R′″ and R″″ groups when morethan one of these groups is present. When R′ and R″ are attached to thesame nitrogen atom, they can be combined with the nitrogen atom to forma 5-, 6-, or 7-membered ring. For example, —NR′R″ is meant to include,but not be limited to, 1-pyrrolidinyl and 4-morpholinyl. From the abovediscussion of substituents, one of skill in the art will understand thatthe term “alkyl” is meant to include groups including carbon atoms boundto groups other than hydrogen groups, such as haloalkyl (e.g., —CF₃ and—CH₂CF₃) and acyl (e.g., —C(O)CH₃, —C(O)CF₃, —C(O)CH₂OCH₃, and thelike).

As used herein, the term “alkenyl” refers to either a straight chain orbranched hydrocarbon of 2 to 6 carbon atoms, having at least one doublebond. Examples of alkenyl groups include, but are not limited to, vinyl,propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl,1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl,1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl,1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hexatrienyl. Alkenyl groups canalso have from 2 to 3, 2 to 4, 2 to 5, 3 to 4, 3 to 5, 3 to 6, 4 to 5, 4to 6 and 5 to 6 carbons. The alkenyl groups is typically monovalent, butcan be divalent, such as when the alkenyl group links two moietiestogether.

As used herein, the term “alkynyl” refers to either a straight chain orbranched hydrocarbon of 2 to 6 carbon atoms, having at least one triplebond. Examples of alkynyl groups include, but are not limited to,acetylenyl, propynyl, 1-butynyl, 2-butynyl, isobutynyl, sec-butynyl,butadiynyl, 1-pentynyl, 2-pentynyl, 1,3-pentadiynyl, 1,4-pentadiynyl,1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl,1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hexatriynyl. Alkynyl groups canalso have from 2 to 3, 2 to 4, 2 to 5, 3 to 4, 3 to 5, 3 to 6, 4 to 5, 4to 6 and 5 to 6 carbons. The alkynyl groups is typically monovalent, butcan be divalent, such as when the alkynyl group links two moietiestogether.

As used herein, the term “alkoxy” refers to alkyl group having an oxygenatom that either connects the alkoxy group to the point of attachment oris linked to two carbons of the alkoxy group. Alkoxy groups include, forexample, methoxy, ethoxy, propoxy, iso-propoxy, butoxy, 2-butoxy,iso-butoxy, sec-butoxy, tert-butoxy, pentoxy, hexoxy, etc. The alkoxygroups can be further substituted with a variety of substituentsdescribed within. For example, the alkoxy groups can be substituted withhalogens to form a “halo-alkoxy” group.

As used herein, the term “cycloalkyl” refers to a saturated or partiallyunsaturated, monocyclic, fused bicyclic or bridged polycyclic ringassembly containing from 3 to 12 ring atoms, or the number of atomsindicated Monocyclic rings include, for example, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, and cyclooctyl. Bicyclic andpolycyclic rings include, for example, norbornane, decahydronaphthaleneand adamantane. For example, C₃₋₈cycloalkyl includes cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, and norbornane.

As used herein, the term “halo-alkoxy” refers to an alkoxy group havingat least one halogen. Halo-alkoxy is as defined for alkoxy where some orall of the hydrogen atoms are substituted with halogen atoms. The alkoxygroups can be substituted with 1, 2, 3, or more halogens. When all thehydrogens are replaced with a halogen, for example by fluorine, thecompounds are per-substituted, for example, perfluorinated. Halo-alkoxyincludes, but is not limited to, trifluoromethoxy,2,2,2,-trifluoroethoxy, perfluoroethoxy, etc.

As used herein, the term “haloalkyl” refers to alkyl as defined abovewhere some or all of the hydrogen atoms are substituted with halogenatoms. Halogen (halo) preferably represents chloro or fluoro, but mayalso be bromo or iodo. For example, haloalkyl includes trifluoromethyl,flouromethyl, 1,2,3,4,5-pentafluoro-phenyl, etc. The term “perfluoro”defines a compound or radical which has at least two available hydrogenssubstituted with fluorine. For example, perfluorophenyl refers to1,2,3,4,5-pentafluorophenyl, perfluoromethane refers to1,1,1-trifluoromethyl, and perfluoromethoxy refers to1,1,1-trifluoromethoxy.

As used herein, the term “heteroalkyl” refers to an alkyl group havingfrom 1 to 3 heteroatoms such as N, O and S. Additional heteroatoms canalso be useful, including, but not limited to, B, Al, Si and P. Theheteroatoms can also be oxidized, such as, but not limited to, —S(O)—and —S(O)₂—. For example, heteroalkyl can include ethers, thioethers andalkyl-amines.

As used herein, the term “heterocycloalkyl” refers to a ring systemhaving from 3 ring members to about 20 ring members and from 1 to about5 heteroatoms such as N, O and S. Additional heteroatoms can also beuseful, including, but not limited to, B, Al, Si and P. The heteroatomscan also be oxidized, such as, but not limited to, —S(O)— and —S(O)₂—.For example, heterocycle includes, but is not limited to,tetrahydrofuranyl, tetrahydrothiophenyl, morpholino, pyrrolidinyl,pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl,piperazinyl, piperidinyl, indolinyl, quinuclidinyl and1,4-dioxa-8-aza-spiro[4.5]dec-8-yl.

As used herein, the term “aryl” refers to a monocyclic or fusedbicyclic, tricyclic or greater, aromatic ring assembly containing 6 to16 ring carbon atoms. For example, aryl may be phenyl, benzyl ornaphthyl, preferably phenyl. “Arylene” means a divalent radical derivedfrom an aryl group. Aryl groups can be mono-, di- or tri-substituted byone, two or three radicals selected from alkyl, alkoxy, aryl, hydroxy,halogen, cyano, amino, amino-alkyl, trifluoromethyl, alkylenedioxy andoxy-C₂-C₃-alkylene; all of which are optionally further substituted, forinstance as hereinbefore defined; or 1- or 2-naphthyl; or 1- or2-phenanthrenyl. Alkylenedioxy is a divalent substitute attached to twoadjacent carbon atoms of phenyl, e.g. methylenedioxy or ethylenedioxy.Oxy-C₂-C₃-alkylene is also a divalent substituent attached to twoadjacent carbon atoms of phenyl, e.g. oxyethylene or oxypropylene. Anexample for oxy-C₂-C₃-alkylene-phenyl is 2,3-dihydrobenzofuran-5-yl.

As used herein, the term “heteroaryl” refers to a monocyclic or fusedbicyclic or tricyclic aromatic ring assembly containing 5 to 16 ringatoms, where from 1 to 4 of the ring atoms are a heteroatom each N, O orS. For example, heteroaryl includes pyridyl, indolyl, indazolyl,quinoxalinyl, quinolinyl, isoquinolinyl, benzothienyl, benzofuranyl,furanyl, pyrrolyl, thiazolyl, benzothiazolyl, oxazolyl, isoxazolyl,triazolyl, tetrazolyl, pyrazolyl, imidazolyl, thienyl, or any otherradicals substituted, especially mono- or di-substituted, by e.g. alkyl,nitro or halogen. Pyridyl represents 2-, 3- or 4-pyridyl, advantageously2- or 3-pyridyl. Thienyl represents 2- or 3-thienyl. Quinolinylrepresents preferably 2-, 3- or 4-quinolinyl. Isoquinolinyl representspreferably 1-, 3- or 4-isoquinolinyl. Benzopyranyl, benzothiopyranylrepresents preferably 3-benzopyranyl or 3-benzothiopyranyl,respectively. Thiazolyl represents preferably 2- or 4-thiazolyl, andmost preferred, 4-thiazolyl. Triazolyl is preferably 1-, 2- or5-(1,2,4-triazolyl). Tetrazolyl is preferably 5-tetrazolyl.

Preferably, heteroaryl is pyridyl, indolyl, quinolinyl, pyrrolyl,thiazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazolyl, imidazolyl,thienyl, furanyl, benzothiazolyl, benzofuranyl, isoquinolinyl,benzothienyl, oxazolyl, indazolyl, or any of the radicals substituted,especially mono- or di-substituted.

Similarly, substituents for the aryl and heteroaryl groups are variedand are selected from: -halogen, —OR′, —OC(O)R′, —NR′R″, —SR′, —R′, —CN,—NO₂, —CO₂R′, —CONR′R″, —C(O)R′, —OC(O)NR′R″, —NR″C(O)R′, —NR″C(O)₂R′,—NR′—C(O)NR″R′″, —NH—C(NH₂)═NH, —NR′C(NH₂)═NH, —NH—C(NH₂)═NR′, —S(O)R′,—S(O)₂R′, —S(O)₂NR′R″, —N₃, —CH(Ph)₂, perfluoro(C₁-C₄)alkoxy, andperfluoro(C₁-C₄)alkyl, in a number ranging from zero to the total numberof open valences on the aromatic ring system; and where R′, R″ and R′″are independently selected from hydrogen, (C₁-C₈)alkyl and heteroalkyl,unsubstituted aryl and heteroaryl, (unsubstituted aryl)-(C₁-C₄)alkyl,and (unsubstituted aryl)oxy-(C₁-C₄)alkyl.

As used herein, the term “halogen” refers to fluorine, chlorine, bromineand iodine.

As used herein, the term “boronate” refers to esters of boronic acid.Boronates include compounds of the formula R″—B(OR′)₂, where R′ islinked to the compound of interest and R″ can be alkyl, heteroalkyl,cycloalkyl, heterocycloalkyl, aryl or heteroaryl, as described above.Alternatively, the two R″ groups can be combined to form aheterocycloalkyl group. Exemplary boronates include, but are not limitedto, pinacol boronate.

As used herein, the term “contacting” refers to the process of bringinginto contact at least two distinct species such that they can react. Itshould be appreciated; however, the resulting reaction product can beproduced directly from a reaction between the added reagents or from anintermediate from one or more of the added reagents which can beproduced in the reaction mixture.

As used herein, the term “reducing agent” refers to an agent capable ofreducing another compound. The reducing agent can be a metal, an organiccompound, or a complex of a metal and an organic compound. For example,the reducing agent can be lithium naphthalenide. Other reducing agentsinclude one-electron reductants capable of transferring an electron froma metal to an organic compound, forming a radical anion that thenperforms the reduction.

Examples of one-electron reductants include lithium or sodiumnaphthalenide. Other reducing agents include Pd/H₂ and electrochemicalreduction methods.

As used herein, the term “alkali metal” refers to the following elementsof the periodic Li, Na, K, Rb and Cs.

As used herein, the term “quinone” refers to compounds of the followingformula:

where the compounds are optionally substituted. Quinones useful in thepresent invention include, but are not limited to, benzoquinone,naphthoquinone and anthraquinone.

As used herein, the term “salt” refers to acid or base salts of thecompounds used in the methods of the present invention. Illustrativeexamples of pharmaceutically acceptable salts are mineral acid(hydrochloric acid, hydrobromic acid, phosphoric acid, and the like)salts, organic acid (acetic acid, propionic acid, glutamic acid, citricacid and the like) salts, quaternary ammonium (methyl iodide, ethyliodide, and the like) salts. It is understood that the pharmaceuticallyacceptable salts are non-toxic. Additional information on suitablepharmaceutically acceptable salts can be found in Remington'sPharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa.,1985, which is incorporated herein by reference.

Pharmaceutically acceptable salts of the acidic compounds of the presentinvention are salts formed with bases, namely cationic salts such asalkali and alkaline earth metal salts, such as sodium, lithium,potassium, calcium, magnesium, as well as ammonium salts, such asammonium, trimethyl-ammonium, diethylammonium, andtris-(hydroxymethyl)-methyl-ammonium salts.

Similarly acid addition salts, such as of mineral acids, organiccarboxylic and organic sulfonic acids, e.g., hydrochloric acid,methanesulfonic acid, maleic acid, are also possible provided a basicgroup, such as pyridyl, constitutes part of the structure.

III. Compounds

The present invention provides cycloparaphenylene compounds useful forthe preparation of armchair carbon nanotubes. In some embodiments, thecycloparaphenylene compounds can have from 6 to 30 paraphenylene ringsand can be substituted or unsubstituted. In other embodiments, thecompounds can have formula I:

In formula I, each R can independently be hydrogen, halogen, C₁₋₆ alkyl,C₁₋₆ haloalkyl, C₁₋₆ heteroalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₁₋₆ haloalkoxy, —OR^(a), —C(O)R^(a), —C(O)OR^(a), —OC(O)R^(a),—C(O)NR^(a)R^(b), —NR^(a)R^(b), —SR^(a), —N(R^(a))C(O)R^(b),—N(R^(a))C(O)OR^(b), —N(R^(a))C(O)NR^(a)R^(b), —OP(O)(OR^(a))₂,—S(O)₂OR^(a), —S(O)₂NR^(a)R^(b), —CN, cycloalkyl, heterocycloalkyl, arylor heteroaryl, wherein each R^(a) and R^(b) is independently hydrogen,C₁₋₆ alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl.Alternatively, R^(a) and R^(b) are combined with the atoms to which eachis attached to from a heterocycloalkyl or a heteroaryl. In addition, twoR groups on adjacent carbons of formula I can be combined with the atomsto which each is attached to form a C₅₋₈ cycloalkyl or an aryl.Moreover, the compounds of formula I can be of any suitable size. Forexample, subscript n can be from 6 to more than 100.

In some other embodiments, each R group of formula I can independentlybe hydrogen, C₁₋₆ alkyl, C₃₋₈ cycloalkyl or aryl. Alternatively, two Rgroups on adjacent carbons of formula I can be combined with the atomsto which each is attached to form a C₅₋₈ cycloalkyl or an aryl. Inaddition, subscript n of formula I can be an integer from 6 to 30. Instill other embodiments, each R group is hydrogen.

In other embodiments, subscript n can be 6, 9, 12, 15, 18, 21, 24, 27 or30. In still other embodiments, subscript n can be 9, 12 or 18. In yetother embodiments, each R can be hydrogen and subscript n can be 9, 12or 18.

The present invention also provides compounds of formula II:

In some embodiments, each R¹ of formula II can independently behydrogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ heteroalkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(a)R^(b), —P(O)(OR^(a))₂,cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein R^(a) andR^(b) are as defined above. In other embodiments, each R¹ of formula IIcan be hydrogen, C₁₋₆ alkyl, C₁₋₆ heteroalkyl, C₃₋₈ cycloalkyl,heterocycloalkyl, aryl or heteroaryl. Moreover, subscript m can be aninteger from 2 to 10. In some other embodiments, each R¹ of formula IIcan be C₁₋₆ alkyl. In still other embodiments, each R¹ of formula II canbe methyl. In yet other embodiments, subscript m of formula II can be 3,4 or 6. In still yet other embodiments, each R¹ of formula II can bemethyl, and subscript m can be 3, 4 or 6.

In some other embodiments, the present invention provides compounds offormula IIa:

In formula IIa, the R¹ groups and subscript m can be as defined above.In addition, the dashed lines of formula IIa can optionally be a bond.

In another embodiment, the present invention provides compounds offormula IIb:

Each R³ and R⁴ can independently be hydrogen, halogen, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ heteroalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆haloalkoxy, —OR^(a), —C(O)R^(a), —C(O)OR^(a), —OC(O)R^(a),—C(O)NR^(a)R^(b), —NR^(a)R^(b), —SR^(a), —N(R^(a))C(O)R^(b),—N(R^(a))C(O)OR^(b), —N(R^(a))C(O)NR^(a)R^(b), —OP(O)(OR^(a))₂,—S(O)₂OR^(a), —S(O)₂NR^(a)R^(b), —CN, cycloalkyl, heterocycloalkyl, arylor heteroaryl, wherein each R^(a) and R^(b) are as defined above.Alternatively, R³ or R⁴ groups on adjacent carbons can be combined withthe atoms to which each is attached to form a cycloalkyl,heterocycloalkyl, aryl or heteroaryl. Moreover, each dashed line canoptionally be a bond in formula IIb.

In some other embodiments, the present invention provides compounds offormula III:

Each R¹ of formula III can be as defined above. Moreover, each R² canindependently be a halogen or a boronate. Radical R² can also include atri-alkyl tin. In yet other embodiments, the present invention providescompound of formula IIIa:

Radicals R¹ and R² of formula IIIa are as described above. In addition,each dashed line of formula IIIa is optionally a bond. In still otherembodiments, the present invention provides compounds of formula IIIb:

Radicals R¹, R², R³, R⁴ and R⁵ of formula IIIb are as described above.In addition, each dashed line of formula IIIa is optionally a bond.

Any boronate is useful in the compounds of the present invention. Forexample, some boronates useful in the compounds of the present inventioninclude those of the following formula:

where each R′ can independently be hydrogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl,C₁₋₆ heteroalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ haloalkoxy,cycloalkyl, heterocycloalkyl, aryl or heteroaryl. Alternatively, the twoR′ groups can be combined with the atoms to which each is attached tofrom a heterocycloalkyl. In some embodiments, the boronate is pinacolboronate (Bpin).

In other embodiments, each R¹ can be methyl and each R² can be iodo. Insome other embodiments, each R¹ can be methyl, and each R² can bepinacol boronate.

The compounds of the present invention also include the salt forms andisomers thereof.

IV. Methods of Making the Compounds

The compounds of the present invention can be prepared by any methodknown in the art. For example, compounds of formula I can be prepared bycoupling a 1,4-dihalophenyl compound with a benzoquinone to form thecoupled compound 1,4-bis(4-halophenyl)cyclohexa-2,5-diene-1,4-diol. The1,4-dihalophenyl compound can be substituted with any suitable R⁴ groupas described above. In some embodiments, the halogen is iodo or bromo.In other embodiments, the 1,4-dihalophenyl is 1,4-diiodophenyl.Likewise, the benzoquinone can be substituted with from 1 to 4 R³ groupsdescribed above. Other benzoquinone groups suitable for the methods ofthe present invention include anthraquinone.

The 1,4-dihydroxy groups of the coupled compound can then be alkylatedby any method known to one of skill in the art. The product of couplingthe 1,4-dihalo phenyl and the benzoquinone is a compound of formula III,described above.

In some embodiments, the benzoquinone can be partially or fullysaturated, i.e., a 1,4-cyclohex-2-ene-dione or 1,4-cyclohexadione,optionally substituted with 1-8 R³ groups described above, to prepare acompound of formula IIIa or IIIb.

The halo groups of R² of the compounds of formula III, IIIa or IIIb canthen be converted to boronates using any means known in the art. Forexample, replacing the halo group with a lithium anion followed byreaction with a borate ester will provide the desired boronate. In someembodiments, the borate ester is isopropyl pinacol borate, providing theproduct pinacol boronate.

Compounds of formulas II, IIa and IIb can be prepared a variety ofmethods known to one of skill in the art. For example, reacting thecompounds of formula III, IIIa or IIIb where R² is halogen withcompounds of formula III, IIIa or IIIb where R² is a boronate, using ametal catalyst under Suzuki coupling conditions can afford compounds offormulas II, IIa and IIb. Other methods of coupling the halogen andboronate compounds of formulas III, IIIa and IIIb are known to one ofskill in the art, such as a Stille coupling or the dimerization of arylhalides. A Stille coupling involves an aryl tin and an aryl halide,using a suitable catalyst. For example, Richard C. Larock, ComprehensiveOrganic Transformations 1989, VCH Publishers, Inc., describes severalcoupling methods useful for making the compounds of the presentinvention.

The compounds of formula II and IIa are then aromatized using methodsknown to one of skill in the art. For example, the compounds of formulaII can be aromatized using a reducing agent such as a one-electronreductant. One-electron reductants useful in the methods of the presentinvention include lithium naphthalenide. Other one-electron reductantsuseful in the methods of the present invention can be formed from analkali metal such as Li, Na, K, Rb and Cs, and an aryl such as phenyl,naphthalene, and anthracene, among others.

The methods of the present invention can be practiced using a variety ofsuitable solvents, concentrations, temperatures, and other reactants.For examples, solvents useful in the methods of the present inventioninclude, but are not limited to, tetrahydrofuran (THF), dioxane,toluene, benzene, methanol, ethanol, hexanes, diethylether, methylenechloride and chloroform. The methods of the present invention can bepracticed at any suitable temperatures, such as from −100° C. to 100° C.

In some embodiments, the present invention provides a method ofpreparing a compound of formula I, wherein each R of formula I can behydrogen, and subscript n can be an integer of 6, 9, 12, 15, 18, 21, 24,27 or 30. The method includes the step of contacting a reducing agentand a compound of formula II, wherein each R¹ of formula II can behydrogen, C₁₋₆ alkyl, C₁₋₆ heteroalkyl, C₃₋₈ cycloalkyl,heterocycloalkyl, aryl or heteroaryl, and subscript m of formula II canbe an integer from 2 to 10. Thus, the compound of formula I is prepared.

The reducing agent can be any agent that reduces the cyclohexadiene ringof formula II to form a phenylene ring. Suitable reducing agentsinclude, but are not limited to one-electron reductants. In someembodiments, the reducing agent can be a one-electron reductant. Inother embodiments, the reducing agent can include an alkali metal and anaryl group. Alkali metals include Li, Na, K, Rb and Cs. Aryl groups aredefined above, and include, but are not limited to, phenyl, naphthyl,anthracene, and phenanthrene. In some other embodiments, the reducingagent includes a naphthalenide. In still other embodiments, the reducingagent is a one-electron reducing agent such as lithium naphthalenide.Other reducing agents are useful in the present invention.

The method of preparing compounds of formula I can also include thepreparation of compounds of formula II, by contacting a benzoquinone and1,4-diiodobenzene to prepare a compound of formula III. In formula III,each R¹ can be C₁₋₆ alkyl, and each R² can independently be iodo or aboronate. The method includes the step of contacting a plurality ofcompounds of formula III, wherein each R² is iodo for at least onecompound of formula III and each R² is a boronate for at least onecompound of formula III. Thus, the compound of formula II can beprepared.

Similarly, the present invention provides a method of preparing acompound of formula IIa. In formula IIa, each R¹ can independently behydrogen, C₁₋₆ alkyl, C₁₋₆ heteroalkyl, C₃₋₈ cycloalkyl,heterocycloalkyl, aryl or heteroaryl. Each dashed line of formula IIacan optionally be a bond, and subscript m can be an integer from 2 to10. The method of preparing a compound of formula IIa includescontacting a plurality of compounds of formula IIIa, where each R² canindependently be a halogen or a boronate. Thus, the compound of formulaIIa is prepared.

In some embodiments, the contacting step includes at least one compoundof formula IIIa where each R² is a halogen and at least one compound offormula IIIa where each R² is a boronate. In other embodiments, thecontacting step includes a plurality of compounds where one R² is ahalogen and one R² is a boronate. Moreover, each dashed line of formulaIIIa can be a bond.

V. Examples

General Experimental Details.

¹H NMR spectra were recorded at 500 MHz on a Bruker Biospin Avance IIHigh Performance Spectrometer and were referenced to residual solventpeaks. ¹³C NMR spectra were recorded at 125 MHz on Bruker Biospin AvanceII High Performance Spectrometer. Infrared spectra were recorded on aVarian 3100 FT-IR Spectrometer. UV/vis spectra were recorded using aPerkin Elmer Lambda 35 UV/Vis Spectrometer. Fluorescence spectra wererecorded using a Jobin Yvon FluoroMax-4 Spectrofluorometer. All reagentswere obtained commercially and purified prior to use. Tetrahydrofuran,diethyl ether, dichloromethane, and toluene were dried by filtrationthrough alumina according to the methods described by Grubbs et al.(Organometallics 1996, 15, 1518-1520). Column chromatography wasperformed using a Biotage SP1 Flash Chromatography System. Thin layerchromatography (TLC) was performed on Whatman 250 μm layer silica gelplates. Developed plates were visualized using p-anisaldehyde, potassiumpermanganate, I₂ stains and UV light. All glassware was flame-dried andcooled under an inert atmosphere of nitrogen unless otherwise stated.Moisture sensitive reactions were carried out under an inert atmosphereof nitrogen using standard syringe/septa techniques.

Example 1 Preparation of 4

Diiodobenzene (31.3 g, 94.9 mmol, 2.05 equiv) was dissolved in 1 L oftetrahydrofuran and cooled to −78° C. To this solution was added a 2.5 Msolution of n-butyllithium in hexanes (41 mL, 102 mmol, 2.2 equiv) over15 min. The reaction mixture was allowed to stir for 30 min.Benzoquinone (5.00 g, 46.3 mmol, 1 equiv) was then added to the reactionas a solid in three equal portions. The solution was stirred for 1.5 hand then added to 500 mL of water with stirring. The mixture was furtherdiluted by the addition of 500 mL of diethyl ether. The biphasic mixturewas allowed to stir for an additional 1 h and then the layers wereseparated. The aqueous layer was extracted with diethyl ether (3×300 mL)and the combined organic layers were washed with a saturated brinesolution (300 mL). The organics were then dried over magnesium sulfateand concentrated in vacuo delivering the diol, which was carried forwardwithout further purification.

To a dry 1-L round bottom flask was added 150 mL of tetrahydrofuran and4.60 g of sodium hydride (116 mmol, 2.5 equiv). The mixture was thencooled to 0° C. and the crude diol was added as a solution in 50 mL oftetrahydrofuran. The mixture was stirred for 30 min whereupon neatmethyl iodide (11.5 mL, 185 mmol, 4 equiv) was added. The mixture wasallowed to warm to rt and stirred for an additional 16 h. The excesssodium hydride was then quenched by addition of 300 mL of water and thismixture was further diluted by addition of 200 mL of diethyl ether. Thelayers were separated and the aqueous layer was extracted with diethylether (3×150 mL). The combined organics were then washed with asaturated brine solution (150 mL) and dried over magnesium sulfate. Theorganics were then concentrated in vacuo delivering crude diiodide 4.The material was further purified by passing the crude mixture through ashort plug of silica gel using 20% ethyl acetate/hexanes as the mobilephase. This technique was effective in removing tlc-baseline materialthat was problematic in recrystallization attempts. Concentration of theeluent then delivered a yellow solid that could be recrystallized fromhot hexanes producing white, crystalline diiodide 4 (8.57 g, 34%): IR(neat) 2937, 2821, 1480, 1082, 818 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.65(d, J=9.0 Hz, 4H), 7.12 (d, J=9.0 Hz, 4H), 6.07 (s, 4H), 3.41 (s, 6H);¹³C NMR (125 MHz, CDCl₃) δ 142.9, 137.4, 133.2, 127.9, 93.4, 74.4, 52.0;HRMS (FAB) m/z calcd for C₂₀H₁₈I₂O₂(M)⁺ 543.9396, found 543.9406.

Example 2 Preparation of 5

Diboronate 5.

Diiodide 4 (3.00 g, 5.51 mmol, 1 equiv) was dissolved in 60 mL oftetrahydrofuran and cooled to −78° C. To this solution was added a 2.5 Msolution of n-butyllithium in hexanes (4.84 mL, 12.1 mmol, 2.2 equiv)over 2 min. Immediately after addition of the alkyl lithium reagent,neat isopropyl pinacol borate (4.50 mL, 22.0 mmol, 4 eq) was addedrapidly and the solution was stirred for 30 min. Water (25 mL) was thenadded to the solution and the biphasic mixture was allowed to stir for15 min at rt. The layers were then separated and the aqueous layer wasextracted with ethyl acetate (3×15). The combined organic layers werewashed with a saturated brine solution and then dried over magnesiumsulfate. The organics were then concentrated in vacuo to deliver ayellow solid which could be further purified by recrystallization fromhot ethyl acetate (2.46 g, 82%): IR (neat) 2978, 2361, 1610, 1361 cm⁻¹;¹H NMR (500 MHz, CDCl₃) δ 7.76 (d, J=8.3 Hz, 4H), 7.41 (d, J=8.3 Hz,4H), 6.10 (s, 4H), 3.44 (s, 6H), 1.35 (s, 24H); ¹³C NMR (125 MHz, CDCl₃)δ 146.3, 134.9, 133.3, 125.3, 83.8, 75.0, 52.0, 24.8, C-B signal notobserved; HRMS (FAB) m/z calcd for C₃₂H₄₂B₂O₆(M)⁺ 544.3168, found544.3183

Example 3 Preparation of 6, 7 and 8

Diiodide 4 (250 mg, 0.46 mmol, 1 equiv), diboronate 5 (250 mg, 0.46mmol, 1 equiv), cesium carbonate (750 mg, 2.30 mmol, 5 equiv), andtetrakis(triphenylphosphine)palladium (50 mg, 0.046 mmol, 0.1 equiv)were dissolved in 33 mL of 10:1 toluene/methanol. The solution wasdegassed using standard freeze/pump/thaw technique (3×) and then heatedto 80° C. for 16 h. After cooling to rt, the mixture was filteredthrough a short plug of Celite and then concentrated. The crude materialwas redissolved in dichloromethane and again filtered through a shortplug of Celite. After concentration, the material was purified using aBiotage SP1 Flash Chromatography System (0 to 20% ethylacetate/dichoromethane gradient). The macrocycles eluted in order ofincreasing size, delivering macrocycle 6 (4 mg, 2%), macrocycle 7 (51mg, 10%), and macrocycle 8 (78 mg, 10%).

6: IR (neat) 2975, 1620, 1350 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.47 (m,24H), 6.17 (s, 12H), 3.48 (s, 18H); LRMS (FAB) m/z calcd forC₅₉H₅₁O₅(M-CH₃O)⁺ 839, found 839.

7: IR (neat) 2975, 1621, 1082 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.49 (m,32H), 6.17 (s, 16H), 3.48 (s, 24H); ¹³C NMR (125 MHz, CDCl₃) δ 142.4,140.0, 133.4, 127.1, 126.4, 74.7, 52.0; LRMS (FAB) m/z calcd forC₇₉H₆₉O₇ (M-CH₃O)⁺ 1129, found 1129.

8: IR (neat) 2971, 1619, 1082, 818 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.50(m, 48H), 6.16 (s, 24H), 3.47 (s, 36H); ¹³C NMR (125 MHz, CDCl₃) δ142.5, 139.9, 133.3, 127.1, 74.6, 52.0; LRMS (FAB) m/z calcd forC₁₁₉H₁₀₅O₁₁ (M-CH₃O)⁺ 1709, found 1709.

Example 4 Preparation of 9

Lithium wire coated with mineral oil (35 mg, 5.0 mmol) was hammered intoa sheet and cut into thin strips. The strips were then quickly rinsedwith hexanes and added to a dry round bottom flask equipped with a glassstir bar. To this was added naphthalene (10 mg, 0.08 mmol) and 5 mL oftetrahydrofuran and the solution was cooled to 0° C. Within 15 min, thesolution turned a dark green color and was then cooled to −78° C. Tothis solution was added macrocycle 7 (5 mg, 0.009 mmol) in 1 mL oftetrahydrofuran. The mixture was stirred for 15 min and then the excesslithium reagent was quenched by the addition of 3 mL of methanol. Atthis time, the excess lithium pieces were removed from the flask and setaside. The solution was then allowed to warm to rt and water (10 mL) anddichloromethane (10 mL) were added. The biphasic mixture was thenseparated and the aqueous layer was extracted with dichloromethane (3×5mL). The combined organics were then dried over magnesium sulfate andconcentrated in vacuo to deliver a yellow solid. This solid could bewashed with hexanes in order to remove the excess naphthalene. Followingthis, the crude material was purified using a Biotage SP1 FlashChromatography System (0 to 40% dichloromethane/hexanes gradient)delivering 1.8 mg (43%) of carbon nanohoop 9 delivering ayellowish-white, amorphous solid: IR (neat) 2923, 2852, 1484, 816 cm⁻¹;¹H NMR (500 MHz, CDCl₃) δ 7.53 (s, 24H); ¹³C NMR (125 MHz, CDCl₃) δ137.9, 127.4; MALDI-TOF m/z calcd for C₅₄H₃₆ (M)⁺ 684.2, found 684.2.

Example 5 Preparation of 10

The general procedure from above was followed delivering 4.2 mg (52%) ofcarbon nanohoop 10 as a white, amorphous solid: IR (neat) 2923, 2852,1462, 812 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.62 (s, 48H); ¹³C NMR (125MHz, CDCl₃) δ 138.5, 127.3; MALDI-TOF m/z calcd for C₇₂H₄₈ (M)⁺ 912.3,found 912.3.

Example 6 Preparation of 11

The general procedure from above was followed delivering 1.6 mg (36%) ofcarbon nanohoop 11 as a white, amorphous solid: IR (neat) 2922, 2851,1462, 808 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.71 (s, 72H); ¹³C NMR (125MHz, CDCl₃) δ 139.0, 127.3; MALDI-TOF m/z calcd for C₁₀₈H₇₂ (M)⁺ 1368,found 1368.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, one of skill in the art will appreciate that certainchanges and modifications may be practiced within the scope of theappended claims. In addition, each reference provided herein isincorporated by reference in its entirety to the same extent as if eachreference was individually incorporated by reference. Where a conflictexists between the instant application and a reference provided herein,the instant application shall dominate.

1.-13. (canceled)
 14. A method of preparing a compound of formula I:

wherein each R is hydrogen, and subscript n is an integer selected fromthe group consisting of 6, 9, 12, 15, 18, 21, 24, 27 and 30, the methodcomprising: contacting a reducing agent and a compound of formula II:

wherein each R¹ is independently selected from the group consisting ofhydrogen, C₁₋₆ alkyl, C₁₋₆ heteroalkyl, C₃₋₈ cycloalkyl,heterocycloalkyl, aryl and heteroaryl, and subscript m is an integerfrom 2 to 10, thereby affording the compound of formula I.
 15. Themethod of claim 14, wherein the reducing agent comprises a one-electronreductant.
 16. The method of claim 14, wherein the reducing agentcomprises an alkali metal and an aryl group.
 17. The method of claim 14,wherein the reducing agent comprises a naphthalenide.
 18. The method ofclaim 14, wherein the method further comprises: contacting abenzoquinone and 1,4-diiodobenzene to prepare a compound of formula III:

wherein each R¹ is C₁₋₆ alkyl, each R² is independently selected fromthe group consisting of iodo and a boronate; and contacting a pluralityof compounds of formula III, wherein each R² is iodo for at least onecompound of formula III and each R² is a boronate for at least onecompound of formula III, to prepare a compound of formula II. 19.-22.(canceled)
 23. The method of claim 14, wherein subscript n is selectedfrom the group consisting of 9, 12, 15, 18, 21, 24, 27, and 30, andwherein subscript m is an integer from 3 to 10.